Mammalian target of rapamycin (mTOR) pathways in neurological diseases

Biomed J. Mar-Apr 2013;36(2):40-50. doi: 10.4103/2319-4170.110365.

Abstract

The mammalian target of rapamycin (mTOR) pathway is an essential cellular signaling pathway involved in a number of important physiological functions, including cell growth, proliferation, metabolism, protein synthesis, and autophagy. Dysregulation of the mTOR pathway has been implicated in the pathophysiology of a number of neurological diseases. Hyperactivation of the mTOR pathway, leading to increased cell growth and proliferation, has been most convincingly shown to stimulate tumor growth in the brain and other organs in the genetic disorder, tuberous sclerosis complex (TSC). In addition, mTOR may also play a role in promoting epileptogenesis or maintaining seizures in TSC, as well as in acquired epilepsies following brain injury. Finally, the mTOR pathway may also be involved in the pathogenesis of cognitive dysfunction and other neurological deficits in developmental disorders and neurodegenerative diseases. mTOR inhibitors, such as rapamycin and its analogs, may represent novel, rational therapies for a variety of neurological disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Epilepsy / drug therapy
  • Epilepsy / metabolism
  • Humans
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / metabolism*
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / metabolism*
  • Tuberous Sclerosis / drug therapy
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / metabolism

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus